All animals adapt to changing environments. A key feature underlying this adaptation process is sensory plasticity, which encompasses a broad range of phenomena from alterations in responsiveness (habituation and sensitization) to more complex forms of associative learning. This proposal describes experiments that examine diet-induced plasticity in taste cells, and how this plasticity produces gustatory habituation in an important neurobiological model, Manduca sexta caterpillars. This phenomenon is of general interest because experience-induced plasticity is a prevalent, but poorly understood, feature of chemosensory systems, and it provides a tool with which to study the biological basis of a complex behavior: food preference. The focus will be on bitter taste because of its importance in poison detection. Preliminary experiments have demonstrated that two days of dietary exposure to a bitter tastant (caffeine) causes a large decrease in responsiveness (i.e., desensitization) of the bitter-sensitive taste cell (or bitter cell) to caffeine. Further, the desensitization of the bitter cell was associated with gustatory habituation to a diet treated with caffeine. These results were collected with a preparation that enables one to make repeated electrophysiological recordings from single taste cells before and after dietary manipulations make comparisons across individual caterpillars using homologous taste cells, and relate desensitization to feeding behavior in the same animal. Based on these experiments, the following specific aims were devised: (i) to determine whether prolonged exposure to any tastant that stimulates the bitter cell will produce both desensitization and gustatory habituation to that same tastant' (ii) to determine whether desensitization and gustatory habituation to one bitter tastant generalize to other bitter tastants, (iii) to determine whether the desensitization response to different bitter tastants is mediated by a common mechanism, and (iv) to determine whether desensitization is controlled by bitter compounds acting on the taste cells either systemically via the blood, directly in the absence of ingestion, or indirectly through centrifugal neural efferents. It is hoped that the proposed studies will reveal something basic about taste receptor systems that will generalize to humans. Such generalizations could provide new insights into the interaction between diet and food preference in humans, and how this interaction may contribute to eating disorders. A better understanding of the connection between intake of bitter foods and bitter sensitivity could also help explain the high rate of ingestion of toxic household substances by humans.